HER2 Positive Breast Cancer

P2, N=17, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Mar 2026

With this technology, we developed trastuzumab deruxtecan, the first DXd-ADC directed toward HER2. Additionally, Dato-DXd showed TROP2-dependent antitumor activity in multiple human cancer cell line-derived and patient-derived xenograft mouse models. Clinically, the global phase III trial targeting hormone receptor-positive, HER2-negative, unresectable or recurrent breast cancer led to its first approval in Japan in December 2024, followed by the approvals in the US and Europe later.

In contrast, TROP2-directed ADCs demonstrate negligible cardiac signals. Given the elevated fatality rate of serious cardiac events associated with T-DXd observed in real-world data, we propose a risk-stratified cardiac monitoring algorithm incorporating high-sensitivity troponin and global longitudinal strain for patients receiving next-generation ADCs.

Present findings are from a small sample cohort and need further validation from a larger cohort. The online version contains supplementary material available at 10.1007/s13193-025-02427-0.

The calibration curves indicated good agreement and DCA confirmed the clinical utility of the model. The proposed nomogram demonstrated robust predictive performance for patients with breast cancer and liver metastases and may provide valuable prognostic information, pending further validation.

Moreover, this "Breast HERV19" expression signature was associated with better prognosis in HR+HER2- eBC, in which its expression was also correlated with biomarkers of sensitivity to anti PD-1 immunotherapy, such as tumor-infiltrating lymphocytes (TILs), PD-L1, and estrogen receptor (ER) expression levels. In eBC, our "Breast HERV19" expression signature makes it possible to isolate a subgroup of HR+HER2- tumors presenting strong immunogenicity, better prognosis, and biological characteristics that suggest a possible benefit from immunotherapy.

Nationwide real-world data demonstrate favorable survival outcomes following adoption of dual anti-HER2 therapy. While these findings are broadly consistent with the CLEOPATRA trial, the observational design does not allow direct assessment of equivalence between studies.

These underscore the relevance of age-related biological factors in shaping breast cancer characteristics. However, among Indonesian women over 45 years old, the proportion of high breast density remains remarkably high (65.6%), suggesting that factors beyond age-such as genetic, hormonal, or lifestyle influences-may contribute to the persistence of dense breast tissue in this population.

Furthermore, the article explores the primary targets of CAR-T cell therapy in the clinical treatment of breast cancer, such as HER2, EGFR, and MUC1, and analyzes the potential and limitations of these targets in therapy. In conclusion, the review outlines significant hurdles in CAR-T cell therapy for breast cancer, such as tumor diversity, the inhibitory tumor milieu, unintended targeting, and cytokine storm, offering strategic solutions to mitigate these obstacles.

P1/2, N=90, Recruiting, Canwell Biotech Limited | Not yet recruiting --> Recruiting

[18F]FDG PET/CT provides significant prognostic information in HER2-low metastatic breast cancer treated with T-DXd. Baseline SULpeak and early PERCIST response enable meaningful risk stratification. The proposed prognostic model requires prospective validation before clinical implementation.

Rhabdomyolysis due to CDK4/6 inhibitor-statin interactions is a rare but potentially life-threatening complication. Vigilant monitoring, timely intervention, and tailored treatment strategies are essential for preventing complications and improving patient outcomes.